tbuckley/cabot-search huggingface dataset:
Abstract P4-03-08: Breast cancer incidence rates in Japan turned into bimodal age distribution in this decade
Authors: Ken Uchida, Hitoshi Ohashi, Hiroko Nogi, Satoki Kinoshita, Ryouko Nosaka, Makiko Kamio
Journal: Cancer Research (2023)

Abstract BACKGROUND: Japan is the globe’s fastest ageing country: 32.0 % of the female population are 65 or older in 2021. The birth rate was 1.30 children per woman in 2021. Japan’s population has been constantly shrinking since 2011 with aging. The number of breast cancer cases has increased rapidly in the course of low birth rate and aging population. Breast cancer has increased and accounted for the first place of all of cancers in Japanese women. OBJECTIVES; Number of breast cancer has increased recently and accounted for the first place of all of female cancers in Japan. Detailed analytics of the increase and aging of breast cancer are not studied. We elucidate the transformation of Japanese breast cancer by ages at diagnosis over the past decade. MATERIALS: We used the registry data of Japanese Breast Cancer Society and Statistics Bureau of Japan in 2018. Female breast cancer new cases were 59,389 patients in 2008 and 93,858 patients in 2018, respectively. The total female population was 65.441 million in 2008 and 64.911 million in 2018, respectively. 65 years and older women accounted for 23.4% in 2008 and 31.0 % in 2018, respectively. METHODS: We compared incidences and incidence rates of breast cancer by ages in 2008 and 2018, respectively. We used the statistical method of Ameijeiras-Alonso et al for mode assessment. RESULTS; Total number of incidences and incidence rates of breast cancer in 2018 were higher than those in 2008 among all ages. Difference of number of incidences were maximum in age of 60-69 in both years. Difference of incidence rates in both years reached maximum in age of 75-79. Incidence rates in 2008 showed unimodal age distribution with the gentle peak. Incidence rates in 2018 showed bimodal age distribution with two peaks of 45-49 and 65-69. CONCLUSIONS; Incidences and incidence rates of breast cancer increased rapidly among all ages in this decade in Japan. The incidence rates increased most in ages of 75-79 and turned into bimodal age distribution in 2018. Citation Format: Ken Uchida, Hitoshi Ohashi, Hiroko Nogi, Satoki Kinoshita, Ryouko Nosaka, Makiko Kamio. Breast cancer incidence rates in Japan turned into bimodal age distribution in this decade. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-08.
Effects of a school-based lifestyle intervention on ideal cardiovascular health in Chinese children and adolescents: a national, multicentre, cluster-randomised controlled trial
Authors: Pengfei Guo, Yueqin Zhou, Yanna Zhu
Journal: The Lancet Global Health (2023)

BackgroundThe prevalence of ideal cardiovascular health among Chinese children and adolescents is alarmingly low. We aimed to examine whether a school-based lifestyle intervention against obesity would improve ideal cardiovascular health.MethodsIn this cluster-randomised controlled trial, we included and randomly assigned schools from the seven regions of China to intervention or control (1:1), stratified by province and school grade (grades 1–11; ages 7–17 years). Randomisation was done by an independent statistician. The 9-month intervention consisted of school promotion for diet, exercise, and self-monitor of obesity-related behaviours and the control group was no promotion. The primary outcome, assessed at both baseline and 9 months, was ideal cardiovascular health (six or more ideal cardiovascular health behaviours [non-smoking, BMI, physical activity, and diet] and factors [total cholesterol, blood pressure, and fasting plasma glucose]). We did intention-to-treat analysis and multilevel modelling. This study was approved by the ethics committee of Peking University, Beijing, China (ClinicalTrials.gov, NCT02343588).Findings30 629 students in the intervention group and 26 581 students in the control group from 94 schools with any follow-up cardiovascular health measures were analysed. At follow-up, 22·0% (1139/5186) of the intervention group and 17·5% (601/3437) in the control group met ideal cardiovascular health. Overall, the intervention was associated with ideal cardiovascular health behaviours (three or more; odds ratio 1·15; 95% CI 1·02–1·29), but not other ideal cardiovascular health metrics after adjusting for covariates. The intervention had higher effects on ideal cardiovascular health behaviours in primary school students aged 7–12 years (1·19; 1·05–1·34) than secondary school students aged 13–17 years (p<0·0001), with no apparent sex difference (p=0·58). The intervention protected senior students aged 16–17 years from smoking (1·23; 1·10–1·37) and improved ideal physical activity in primary school students (1·14; 1·00–1·30) but was associated with lower odds of ideal total cholesterol in primary school boys (0·73; 0·57–0·94).InterpretationThis school-based intervention, focused on diet and exercise, was effective in improving ideal cardiovascular health behaviours in Chinese children and adolescents. Early intervention might benefit cardiovascular health over the life course.FundingThe Special Research Grant for Non-profit Public Service of the Ministry of Health of China (201202010) and Guangdong Provincial Natural Science Foundation (2021A1515010439).
Abstract P5-03-04: PIK3CA mutation prevalence in hormone receptor positive breast cancer patients in United Arab Emirates
Authors: Fathi Azribi, Mohammad Hourani, Sulaman Magdub, Aydah Alawadhi, Ali Yousif, Emad Dawoud, Khaled Al Qawasmeh, Mouza Al Ameri, Diaeddine Trad, Nouri Bennini, Mohamed Ahmed, Jawaher Ansari
Journal: Cancer Research (2023)

Abstract Background: The Phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit alpha (PIK3CA) gene is mutated in about 30-40% of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) breast cancer (BC) patients. For HR+/HER2- advanced breast cancer patients with disease progression following endocrine-based therapy, the NCCN guideline recommends testing for PIK3CA mutations with tumour or liquid biopsy to identify suitable patients for targeted therapy with alpelisib, an oral α-specific PI3K inhibitor in combination with fulvestrant. The primary objective of this study was to evaluate the proportion and distribution of PIK3CA mutational landscape of HR+ve BC patients at the largest cancer centre in the United Arab Emirates (UAE). Material and methods: Retrospective review of consecutive HR+ve BC patients at Tawam Hospital for whom PIK3CA testing was requested. DNA was extracted from the samples and a targeted resequencing assay was used for mutation detection in exons 7, 9 and 20 of the PIK3CA gene. Sequencing was carried out using the Next Generation Sequencing platform Ion GeneStudio S5 Prime System with a detection limit of 2-5% of the mutant allelic content. Results: 124 patients with HR+ve BC were enrolled in the present study. The pathology samples were considered unsuitable/unsatisfactory in 18 cases. The median age was 51.5 years (range 31-90). All patients were female, 54% were post-menopausal and 49% presented with de-novo metastatic disease. Of the 106 eligible patients, PIK3CA mutations were detected in 33 (31%) patients, the most common being H1047R (45%) and E545K (30%) mutations in exons 20 and 9, respectively. Other less common mutations included C420R mutations (6%) in exon 7, E542 (6%) in exon 9 and H1047Y (3%) in exon 20. 9% of patients had more than one hotspot mutations, primarily in exons 9 and 20. Of the 12 HER2 +ve patients tested, 3 had PIK3CA mutations, most commonly the H1047R mutation in exon 20. Conclusion: The prevalence of PIK3CA mutations and the presence of most common hotspot mutations in exons 20 and 9 was consistent with prior published studies. The clinical relevance of PIK3CA mutations in HER2 +ve BC patients needs further assessment. Citation Format: Fathi Azribi, Mohammad Hourani, Sulaman Magdub, Aydah Alawadhi, Ali Yousif, Emad Dawoud, Khaled Al Qawasmeh, Mouza Al Ameri, Diaeddine Trad, Nouri Bennini, Mohamed Ahmed, Jawaher Ansari. PIK3CA mutation prevalence in hormone receptor positive breast cancer patients in United Arab Emirates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-04.
The effect of public policy on high BMI trends of Mexican children: an interrupted time series analysis
Authors: Daniel Bernal-Serrano, David Contreras-Loya, Daniel Choperena-Aguilar, Héctor Arreola-Ornelas, Gustavo Adolfo Merino-Juárez
Journal: The Lancet Global Health (2023)

BackgroundMexico declared an obesity epidemic in 2000, and in response, became an early adopter of public policies in the form of natural experiments, which have not been evaluated for their effect on high BMI. We focus on children younger than 5 years due to the long-term outcomes of childhood obesity.MethodsWe used the Global Burden of Disease data to evaluate time trends in high BMI, defined as being overweight or obese based on the International Obesity Task Force standards, between 1990 and 2019. Marginalisation and poverty estimates from Mexico's Government were used to identify differences in socioeconomic groups. The time variable reflects the introduction of policies between 2006 and 2011. Our hypothesis was that poverty and marginalisation modify the effects of public policies. We tested for the change in prevalence of high BMI over time using Wald-type tests, correcting for the effect of repeated measures. We stratified the sample by gender, marginalisation index, and households under the poverty line. Ethics approval was not required.FindingsBetween 1990 and 2019, high BMI in children younger than 5 years increased from 23·5% (95% uncertainty interval 38·6–14·3) to 30·2% (46·0–20·4). After a period of sustained increase to 28·7% (44·8–18·6) in 2005, high BMI decreased to 27·3% (42·4–17·4; p<0·001) in 2011. Afterwards, high BMI increased constantly. We found an average gender gap of 12·2%, with a higher rate in males, in 2006, which remained constant. With respect to marginalisation and poverty, we observed a reduction in high BMI across all strata, except for the uppermost quintile of marginalisation in which high BMI remained flat.InterpretationThe epidemic affected groups across different socioeconomic levels, thus weakening economic explanations for the decrease in high BMI, while gender gaps point to behavioural explanations of consumption. The observed patterns warrant investigation through more granular data and structural models to isolate the effect of the policy from secular trends in the population, including other age groups.FundingTecnológico de Monterrey Challenge-Based Research Funding Program.
Why do preconception and pregnancy lifestyle interventions show little evidence of success in preventing overweight and obesity in children? A scoping review
Authors: Kaat Philippe, Shevaun Teo, Carla Perrotta, Fionnuala M McAuliffe, Catherine M Phillips
Journal: The Lancet Global Health (2023)

BackgroundAdverse lifestyle factors in the periconception and early life period, including high maternal prepregnancy BMI and excessive gestational weight gain, are important risk factors for childhood obesity. Early prevention is key, but results from systematic reviews of preconception and pregnancy lifestyle interventions have shown mixed success in improving children's weight outcomes and adiposity. We aimed to investigate the complexity of these early interventions and process evaluation components and authors' statements to improve our understanding regarding their limited success.MethodsWe did a scoping review, guided by frameworks of the Joanna Briggs Institute and Arksey and O'Malley. Eligible articles (with no language restriction) were identified between July 11 and Sept 12, 2022, by searching PubMed, Embase, and CENTRAL; consulting previous reviews; and conducting CLUSTER searches. A thematic analysis was conducted with NVivo in which process evaluation components and authors' interpretations were coded as reasons. Intervention complexity was evaluated with the Complexity Assessment Tool for Systematic Reviews.Findings40 publications corresponding to 27 eligible preconception or pregnancy lifestyle trials with child data beyond age 1 month were included. Most interventions started during pregnancy (n=25) and focused on multiple lifestyle factors (eg, diet and exercise). The preliminary results show that almost no interventions involved the participants' partner or social network. Potential reasons for limited success in the interventions preventing overweight or obesity in children included the start time of the intervention, duration and intensity, and sample size or dropout rates. The results will be discussed with an expert group as part of a consultation stage.InterpretationThe results and discussions with an expert group are expected to uncover gaps and inform the design or adaptation of future interventions and approaches to potentially increase success rates in preventing childhood obesity.FundingFunded by the Irish Health Research Board through the transnational JPI HDHL ERA-NET HDHL-INTIMIC-2020 call (PREPHOBES): EU Cofund action (number 727565; EndObesity project).
Abstract P6-11-11: Breast cancer stem cell marker, CD24 regulates metabolic reprogramming in triple negative breast cancer
Authors: Divya Murthy, Debasmita Dutta, Sukjin Yang, Junhyoung Park, Benny Kaipparettu
Journal: Cancer Research (2023)

Abstract Breast cancer stem cell (BCSC) is a subset of cancer cells that can dictate the tumor initiation, metastatic progression, and therapeutic resistance in BC. The eradication of this unusual population is emerging as a new paradigm in cancer treatment. Molecularly, CD24 negativity in conjunction with high expression of CD44 is considered a hallmark for the BCSCs. While extensive studies have been performed to delineate the role of CD44 in BCSCs, the regulation of CD24 and its functional role have not been fully understood. In this study, we investigated the regulatory mechanisms responsible for low CD24 expression in BCSCs and their functional relevance in BCSCs. Analysis of DNA from tumor tissues and blood from BC patients as well as BCSCs sorted from BC cell lines suggest that CD24 is epigenetically regulated via DNMT-1/HDAC1-dependent increased methylation of CpG islands in the CD24 proximal promoter region. To understand the role of CD24 in triple-negative BC (TNBC), an aggressive subgroup of BC, we knocked down (CD24-KD) and overexpressed (CD24-OE) CD24 in metastatic TNBC cells. While CD24-KD resulted in increased proliferation and stemness, CD24-OE diminished the proliferative and stem-like potential. To further identify the signaling cascade underpinning these effects, we performed phospho-proteome analysis using Reverse Phase Protein Array (RPPA). Remarkably, we observed an enhanced activation of AMPK and NF-kB signaling cascades, and reduced PDGFRβ signaling upon depletion of CD24. As signaling cascades are intricately linked to cellular metabolism, we performed a metabolomic analysis of CD24-KD and CD24-OE cells. Our comprehensive analysis revealed heightened activation of mitochondrial fatty acid β-oxidation (FAO) in CD24-KD and increased glutamine metabolism in CD24-OE cells. In coherence with these findings, we observed significant regulation of genes related to fatty acid metabolism in the TNBC patient cohort expressing low levels of CD24. Consistently, the CD24-KD cells demonstrated increased sensitivity towards FAO inhibitors while CD24-OE cells were more sensitive to glutamine metabolism inhibitors. In vivo studies to further understand the translational significance of this metabolic axis is underway. Taken together, our study demonstrates, for the first time, that CD24 presents a novel metabolic vulnerability that can target BCSCs to gain a therapeutic advantage in the treatment of drug-resistant TNBC patients. Citation Format: Divya Murthy, Debasmita Dutta, Sukjin Yang, Junhyoung Park, Benny Kaipparettu. Breast cancer stem cell marker, CD24 regulates metabolic reprogramming in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-11-11.
Abstract P4-03-10: BREAST DENSITY AND RISK OF BREAST CANCER
Authors: Elsebeth Lynge, Ilse Vejborg, Martin Lillholm, Mads Nielsen, George Napolitano, My von Euler-Chelpin
Journal: Cancer Research (2023)

Abstract Background: Early studies reported a 4-6-fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case-control studies, we took advantage of a population-based screening program to study density and breast cancer incidence in a cohort design. Methods: In the Capital Region, Denmark, woman aged 50-69 are invited to screening biennially. Women screened November 2012 - December 2017 were included, and classified by BI-RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RR) and 95% confidence intervals (CI) were compared across density groups using Poisson-regression. Results: We included 189,609 women; 1,067,293 person-years; and 4110 incident breast cancers/DCIS. Thirty-three percent of women had BI-RADS density code 1; 38% code 2; 24% code 3; 4.7% code 4; and missing 0.3%. Using women with BI-RADS density code 1 as baseline; women with code 2 had RR 1.69 (95% CI 1.56-1.84); women with code 3, RR 2.06 (95% CI 1.89-2.25); and women with code 4, RR 2.37 (95% CI 1.05-2.74). Results differed between observations accumulated during screening and above screening age. Conclusions: This cohort study showed a 2.37-fold difference in breast cancer risk between women with highest and lowest breast density. Translated into absolute risk of breast cancer after age 50, this was a 6.2% risk for the one-third of women with lowest density, and 14.7% for the five percent of women highest density. Citation Format: Elsebeth Lynge, Ilse Vejborg, Martin Lillholm, Mads Nielsen, George Napolitano, My von Euler-Chelpin. BREAST DENSITY AND RISK OF BREAST CANCER [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-10.
Abstract P4-03-09: Risk of breast cancer after false-positive mammography recalls: a matched cohort study
Authors: Xinhe Mao, Wei He, Keith Humphreys, Haomin Yang, Kamila Czene
Journal: Cancer Research (2023)

Abstract Background: False-positive mammography recalls are common and associated with an increased risk of subsequent breast cancer. But the long-term risk and whether the risk restricts to the breast cancer detected on the false-positive recalled side remain unclear. Objective: To examine long-term risk of breast cancer after false-positive recalls by side of breasts, mode of detection and tumor characteristics. Design: Matched cohort. Setting: The mammography screening program in Stockholm, Sweden. Participants: We included 45,588 women who received false-positive recalls (1991-2017) and 455,880 matched women who were not recalled, and then followed them until March 31st, 2020. Measurement: Breast cancer incidence; mode of breast cancer detection; tumor characteristics; re-attendance at mammography screening. Results: With Kaplan-Meier curves, we showed that women with false-positive recalls were more likely than those without to have breast cancers, on not only the previously recalled (false-positive) side but also the unrecalled side, up to at least 20 years since the next scheduled screen. We further found that risks were particular higher for breast cancer diagnosed on the false-positive side within first four years of follow-up (hazard ratio [HR]: 2.40; 95% confidence interval [CI]: 2.17-2.65), by the use of stratified Cox model while allowing for time-varying effects. In addition, when stratifying by age at matched mammograms, we found the association was stronger among old women (60-74) than young women (40-59). This was consistent with the result that the risk of breast cancer was higher among women with low density than those with high density. Of note, within the first four years, women with false-positive recalls were at an increased risk of clinical detected cancers (cancer detected among women who did not attend last scheduled screen or were at an age out of screening age ranges) on the false-positive side compared with those who were not recalled. In addition, we found that women with false-positive recalls had statistically significantly lower re-attendance rates at every of next five scheduled screenings. Conclusion: Women with false-positive recalls are at an increased risk of breast cancer for at least two decades, while these women are less likely to adhere to subsequent mammography screens comparing to women who were not recalled. Thus, women with false-positive recalls, especially older women, should be encouraged to re-attend the mammography screening program. Citation Format: Xinhe Mao, Wei He, Keith Humphreys, Haomin Yang, Kamila Czene. Risk of breast cancer after false-positive mammography recalls: a matched cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-09.
Abstract P2-26-21: The Principal Factors Associated with Engraftment Success of Patient-Derived Xenograft of Breast Cancer
Authors: Jongwon Lee, Uk Lee, Hee Jin Lee, Gyungyub Gong
Journal: Cancer Research (2023)

Abstract Background: Patient-derived xenografts (PDXs) are increasingly used in cancer research as tools for studying cancer biology and personalized immunotherapy response. However, a comprehensive evaluation of patient-derived breast cancer xenograft generation rates in various settings is understudied. Methods: We conducted a prospective study of breast cancer patients treated with surgery to generate PDXs. PDXs were characterized by molecular subtypes, specific diagnostic entities, modified Bloom-Richardson system nuclear and histologic grades, treatment with neoadjuvant chemotherapy (NAC), Miller Payne grade, residual caner burden class, invasive tumor size, lymphovascular invasion status, number of positive lymph nodes, and the percentage of tumor infiltrating lymphocytes in the implanted tumors. Results: Three hundred and seventy-two (157 post-chemotherapy, 215 chemo-naïve) patient-derived tumors were implanted and 63 PDXs were established (17.0%). PDX engraftment was higher in the patients with higher nuclear and histologic grades using the modified Bloom-Richardson system (27.6% vs. 3.2%, p = 0.003) and triple negative breast cancer (TNBC) than in those with hormone receptor-positive cancer (36.4% vs. 3.2%, p = 0.02). Tumors from patients who received NAC (30.0% vs. 7.4%, p = 0.05) were also close to being statistically significant for successful PDX generation. Conclusions: PDXs can be established from clinically aggressive breast cancers, especially in patients with high nuclear and histologic grade TNBC treated with NAC. The prediction of engraftment success using these factors would establish cost-effective immunotherapy trials employing PDXs. Citation Format: Jongwon Lee, Uk Lee, Hee Jin Lee, Gyungyub Gong. The Principal Factors Associated with Engraftment Success of Patient-Derived Xenograft of Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-21.